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. 2016 Oct;20(10):1813-20.
doi: 10.1111/jcmm.12869. Epub 2016 Apr 26.

Down-regulation of microRNAs of the miR-200 family and up-regulation of Snail and Slug in inflammatory bowel diseases - hallmark of epithelial-mesenchymal transition

Nina Zidar  1 , Emanuela Boštjančič  2 , Miha Jerala  2 , Nika Kojc  2 , David Drobne  3 , Borut Štabuc  3 , Damjan Glavač  2
Affiliations

Down-regulation of microRNAs of the miR-200 family and up-regulation of Snail and Slug in inflammatory bowel diseases - hallmark of epithelial-mesenchymal transition

Nina Zidar et al. J Cell Mol Med. 2016 Oct.

Abstract

Fibrosis is an important feature of inflammatory bowel diseases (IBD), particularly Crohn's disease (CD), but its pathogenesis is poorly understood. To determine the postulated involvement of epithelial-mesenchymal transition (EMT) in the development of fibrosis in IBD, we analysed the expression profiles of the miR-200 family which has been shown to induce EMT in experimental models and various human diseases. We also analysed the expression of Snail and Slug, postulated targets of the investigated microRNAs. Ten patients with ulcerative colitis (UC) and 10 patients with CD who underwent colon resection were included. From each, two tissue samples were chosen (one with the most severely and one with the least affected or normal mucosa) for analysis of microRNAs expression using real-time polymerase chain reaction, and Snail and Slug expression using immunohistochemistry. We found significant down-regulation of all investigated microRNAs in CD, and of three investigated microRNAs in UC, in comparison to the normal or the least affected mucosa. Comparing UC and CD, four microRNAs were significantly more down-regulated in CD than in UC. Snail and Slug were expressed in the injured epithelium and occasionally in mesothelial cells and submesothelial fibroblasts. Our finding of down-regulation of the miR-200 family and up-regulation of transcription repressors Snail and Slug supports the postulated role of EMT in the pathogenesis of fibrosis in IBD. The described expression patterns are consistent with the notion that fibrosis does not occur only in CD but also in UC, being much more severe in CD.

Keywords: Crohn's disease; Slug; Snail; epithelial−mesenchymal transition; fibrosis; microRNA; ulcerative colitis.

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Figures

Figure 1
Figure 1
Expression of microRNAs of the miR‐200 family in Crohn's disease (A) and ulcerative colitis (B) in comparison to the corresponding normal mucosa. CD, Crohn's disease; UC, ulcerative colitis; *P ≤ 0.05; **P ≤ 0.01.
Figure 2
Figure 2
Expression of microRNAs of the miR‐200 family in Crohn's disease in comparison to ulcerative colitis. CD, Crohn's disease; UC, ulcerative colitis; *P < 0.05; **P ≤ 0.01.
Figure 3
Figure 3
Crohn's disease. (A) Distorted crypt architecture, inflammation in the lamina propria and submucosa. (B) Immunohistochemistry for Snail and Slug: positive nuclear and cytoplasmic reaction for Snail and Slug in the crypt epithelium and some inflammatory cells. (C) Immunohistochemistry for E‐cadherin: positive membraneous reaction in the crypt epithelium, with a focal decreased intensity of staining.
Figure 4
Figure 4
Ulcerative colitis. (A) Distorted crypt architecture, inflammation in the lamina propria and in the upper part of submucosa. (B) Immunohistochemistry for Snail and Slug: positive nuclear and cytoplasmic reaction for Snail and Slug in the crypt epithelium and some inflammatory cells. (C) Immunohistochemistry for E‐cadherin: positive membranous reaction in the crypt epithelium, with a focal decreased intensity of staining.
Figure 5
Figure 5
Crohn's disease. (A) Proliferation of myofibroblasts in the subserosal layer, with a positive immunohistochemistry for Snail and Slug (B).
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